RT Journal Article
T1 Myc overexpression enhances of epicardial contribution to the developing heart and promotes extensive expansion of the cardiomyocyte population
A1 Villa del Campo, Cristina
A1 Lioux, Ghislaine
A1 Carmona, Rita
A1 Sierra, Rocio
A1 Munoz-Chapuli, Ramon
A1 Claveria, Cristina
A1 Torres, Miguel
K1 Vascular smooth-muscle
K1 Wilms-tumor
K1 Progenitors contribute
K1 Coronary-arteries
K1 Endothelial-cells
K1 Wt1 expression
K1 Chick-embryos
K1 Mouse
K1 Adult
K1 Fibroblasts
AB Myc is an essential regulator of cell growth and proliferation. Myc overexpression promotes the homeostatic expansion of cardiomyocyte populations by cell competition, however whether this applies to other cardiac lineages remains unknown. The epicardium contributes signals and cells to the developing and adult injured heart and exploring strategies for modulating its activity is of great interest. Using inducible genetic mosaics, we overexpressed Myc in the epicardium and determined the differential expansion of Myc-overexpressing cells with respect to their wild type counterparts. Myc-overexpressing cells overcolonized all epicardial-derived lineages and showed increased ability to invade the myocardium and populate the vasculature. We also found massive colonization of the myocardium by Wt1Cre-derived Myc-overexpressing cells, with preservation of cardiac development. Detailed analyses showed that this contribution is unlikely to derive from Cre activity in early cardiomyocytes but does not either derive from established epicardial cells, suggesting that early precursors expressing Wt1Cre originate the recombined cardiomyocytes. Myc overexpression does not modify the initial distribution of Wt1Cre-recombined cardiomyocytes, indicating that it does not stimulate the incorporation of early expressing Wt1Cre lineages to the myocardium, but differentially expands this initial population. We propose that strategies using epicardial lineages for heart repair may benefit from promoting cell competitive ability.
PB Nature
SN 2045-2322
YR 2016
FD 2016-09-25
LK http://hdl.handle.net/10668/18910
UL http://hdl.handle.net/10668/18910
LA en
NO Villa Del Campo C, Lioux G, Carmona R, Sierra R, Muñoz-Chápuli R, Clavería C, et al. Myc overexpression enhances of epicardial contribution to the developing heart and promotes extensive expansion of the cardiomyocyte population. Sci Rep. 2016 Oct 18;6:35366. doi: 10.1038/srep35366. Erratum in: Sci Rep. 2016 Dec 09;6:37880
NO We thank V. García for mouse work, E. Arza and A.M. Santos for help with microscopy, R. Nieto and J. Ligos for help with cytometry and Paul Riley for critical reading of the manuscript. This work was supported by grants BFU2012-31086 and ISCIII-RD12/0019/0005 (ISCIII) to MT and BFU2014-52299 and ISCIII-RD12/0019-0022 to RM from the Spanish Ministry of Economy and Competition (MINECO) and grants P2010/BMD-2315 from the Madrid Regional Government to MT and P11-CTS-07564 from the Junta de Andalucía to RM. C.V. was supported by a FPI grant from the MINECO. The CNIC is supported by the MINECO and the Pro-CNICFoundation.
DS RISalud
RD Apr 10, 2025